The role of adult hippocampal neurogenesis in brain health and disease

Abstract

Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes. Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions, such as memory encoding and mood regulation. In addition, several brain diseases, such as neurological diseases and mood disorders, have deleterious effects on adult hippocampal neurogenesis, and some symptoms of those diseases can be partially explained by the dysregulation of adult hippocampal neurogenesis. Here we review a possible link between the physiological functions of adult-born neurons and their roles in pathological conditions.

Figure 1. Development of adult-born DGCs and the trisynaptic circuit in the hippocampus

(a) The trisynaptic neural circuit in the hippocampus from the entorhinal cortex through the dentate gyrus, CA3 and CA1. (b) Developmental processes of adult hippocampal neurogenesis. Adult neural stem cells in the hippocampus (radial glia-like cells, Type 1 cells) and their differentiation through intermediate progenitors to mature DG neurons.

Figure 2. Somatic mosaicism during adult neurogenesis drives functional heterogeneity

(a) Adult-born neurons are generated in the subgranular zone of the dentate gyrus; during this period of maturation they are prone to DNA damage, replication stress, and retrotransposition. Neuron A (green), B (purple), and C (orange) represent three distinct adult-born neurons. (b) Each newborn neuron will have a unique complement of neurogenesis-driven mutations. Each tick mark represents a unique mutation in the respective neuron such as an aneuploidy event, a CNV, or a newly inserted retrotransposon. (c) Depending on the complement of mutations, the neuron may be shifted further away from the mean function of all dentate granule neurons, thereby increasing diversity within the DG.